Stimulation of monocyte cGMP by leukocyte dialysates. An antigen-independent property of dialyzable transfer factor.

Abstract

A B S T R A C T We studied the effects of dialysates from leukocyte lysates containing dialyzable transfer factor activity and other leukocyte dialysates devoid of transfer factor activity on accumulation of cyclic nucleotides in human leukocytes. Dialysates from normal leukocytes produced 4-to 11-fold increases in leukocyte cGMP, and experiments with purified cell populations revealed that the increases were predominantly, if not entirely, in blood monocytes. Substances that increased monocyte cGMP could be obtained from several cell populations including mononuclear cells from HypaqueFicoll gradients, plastic-adherent monocytes, nonadherent lymphocytes, and neutrophils, but were not present in dialysates of leukemic lymphocytes from patients with the Sezary syndrome. Moreover, dialysates that increased leukocyte cGMP had essentially no effect on intracellular cAMP.Dialysates of lysed mononuclear cells contained serotonin, ascorbate, and an unidentified cholinergic activity, agents known to increase leukocyte cGMP. After passage of dialyzable transfer factor from mononuclear cells through a gel-filtration column, four fractions were obtained that increased leukocyte cGMP. Two of these fractions contained ascorbate; two other active fractions, including one that also caused conversion of delayed skin tests, did not contain detectable ascorbate or serotonin. The dialysate of lysed neutrophils also increased cGMP, but this activity was limited to the column fractions which contained ascorbic acid.These observations raise the possibility that alterations in monocyte cGMP content could modulate either the

Dialyzable Leukocyte Extract differentially regulates the production of TNF?, IL-6, and IL-8 in bacterial component-activated leukocytes and endothelial cells

“…We also observe a similar effect in LPS-stimulated monocytes. In earlier studies with DLE, other groups reported accumulation of cyclic nucleotides by DLE in lymphocytes and monocytes [13,30]. Our findings support the notion that the increase of cAMP induced by DLE could be related to the DLE effect on proinflammatory cytokine production.…”

Reactions in Canine Skin with Human Leukocyte Lysates

“…The three to five peaks are individually recombined, lyophilized, and refiltered. Peak IV elutes at 1.6 (v/v) glucose, has a high 260/280 ratio, and appears similar to TF fractions described by Zuckerman et al (4), as well as Sandler et al (5). Analyses of this fraction have shown it to transfer skin reactions in men, and to contain hypoxanthine, a variable amount of orcinol-re-This investigation was supported in part by General Research Support Grant RR05402 from the General Research Support Branch, Division of Research Resources, National Institutes of Health.…”

Impaired insulin-mediated glucose uptake in monocytes of short children with intrauterine growth retardation

“…A modified two‐stage process for monocyte isolation was undertaken that incorporated histopaque separation followed by adherence (25). A 10–20 mL blood sample was collected from subjects into heparinized tubes and histopaque separation performed within 1 h of blood collection.…”